Defeating Depression by Reconnecting With Others and the World

The opinions expressed by Psychiatry & Behavioral Health Learning Network bloggers and those providing comments are theirs alone and are not meant to reflect the opinions of the publication.

A few months ago, I was musing about the benefits of disconnecting from others to rediscover my inner world. Then in October, this year’s Psych Congress returned, time and again, to the theme of us needing to reconnect with a larger experience of the world in order to find a path out of depression.

Psych Congress cochair Charles Raison, MD, set the tone in his preconference talk, “Blast from the past: Understanding ancient mind-body causes of depression to optimize 21st century treatment,” explaining that it is the loss of access to the proximal means of evolutionary success that is often depressogenic. In short, he pointed out that when we are cut off from a meaningful and generative connection with others, we become depressed.

Featured Speaker Robin Carhart-Harris, PhD, came from Oxford, England to share his research on psilocybin as an antidepressant, an effort now moving into phase 3 trials fast-tracked by the FDA. Using sophisticated neuroimaging to better understand the psychedelic state, he shared his “entropic brain” model1 that maps the flexibility or rigidity of brain states onto our existing taxonomic understanding of mental illness.

To oversimplify, some psychiatric illnesses such as depression or addiction, can be seen as states of low entropy—the probability of change is low, and the likelihood that the “stuck” behavior will continue into the future is high. The psychedelic state is a transient state of high entropy in which these ossified networks are disrupted to return to a more supple and open state in which some of these previously “stuck” behaviors can be shifted, assisting and accelerating psychotherapy. Curiously, as his and other studies2 found, that the degree of antidepressant response was correlated with the intensity of a quality known as “oceanic boundlessness” during the psychedelic experience—a deeply felt sense of interconnection with the larger world beyond our individual egos.3

I spoke of the phenomenological experience of depression as one of disconnection, highlighting research from Dr. Carhart-Harris’ colleague, Rosalind Watts, DClinPsy4 at Imperial College, London. In her important qualitative work, depression is seen as a state of profound disconnection—from others, from sensory pleasure, from self (in the form of self-loathing), and from the ability to shift readily from inner to outer worlds (the person with depression is trapped on a hamster wheel of rumination); that is often made worse by our existing antidepressant treatments that can worsen anhedonia (in the form of worsened apathy and sexual dysfunction) and restrict emotional range. The therapeutic psychedelic experience, albeit brief, may have the capacity to disrupt this rigidity in such a way that lasts long after the drug’s effects have passed.

Esketamine, closing in on FDA approval, and its racemic originator, ketamine, were the subject of several sessions. While the qualitative narrative of ketamine has assumed a more neurobiological mantle than its psychedelic cousins, the dominant explanatory model has been one of rapid neurogenesis and dendritic branching due to disinhibition of mTOR growth pathways. Even on a cellular level, rapid antidepressant responses are marked by our very cells reaching out to connect more robustly with their neighbors.

Carhart-Harris closed by discussing how the action of psilocybin is dependent on the serotonin 2A receptor. Asking the question, “why have humans evolved to have such a receptor?” he noted that this receptor has been conserved by evolution as a mechanism though which humans have been able to significantly adapt their outlook and behaviors at times of significant tumult and change.

We may indeed be living in a time, in which disconnection, isolationism, and tribalism feel increasingly the norm, and it was heartening to see psychiatry both describing the mechanism of, and leading the charge towards reunion and reconnection, both individually and collectively, as a path to help heal our patients and the world which we all inhabit.